Mechanisms of vertebrate post-embryonic developmental progression

脊椎动物胚胎后发育进程的机制

• 批准号: 9440774
• 负责人: Sarah Kelly McMenamin
• 金额: $ 22.66万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9440774
• 关键词: Mechanisms; vertebrate; post; embryonic; developmental

ABSTRACT We still know very little about the mechanisms that regulate and synchronize morphogenetic events during later stages of vertebrate development. Nonetheless, understanding the factors controlling these later developmental periods is essential to understanding how adult traits form, and will lend insight into morphological defects and disorders that arise during human post-embryonic fetal and neonatal periods. This research utilizes the zebrafish, which undergoes extensive post-embryonic development involving modifications and maturation in many different organ systems; many of these changes are similar or identical to processes that occur following embryogenesis in humans. This proposal employs several strategies towards understanding the mechanisms underlying the zebrafish transformation from larva to juvenile. The first aim adopts a targeted approach, testing the specific roles of thyroid hormone in post-embryonic developmental transitions. Multiple lines of evidence indicate that thyroid hormone is involved in several developmental processes in zebrafish, but the ability of this hormone to effect specific morphogenetic processes and cellular behaviors remains unclear. This aim will test roles of thyroid hormone in promoting both global somatic developmental progression and the behaviors of a specific, well-characterized cell lineage that produces adult pigmentation during the larval-to-juvenile transition. The second aim takes a forward genetic strategy to identify novel genes required for post-embryonic stage transitions. This approach has already identified two mutants that exhibit complete somatic arrest during larval development, ceasing ontogenetic progression at stages normally reached by 2- and 3-week old wild-type larvae. These phenotypes suggest an impairment of genes absolutely required for post-embryonic progression. Mapping and cloning the mutations and characterizing the pathways to which they belong will reveal mechanisms essential for post-embryonic developmental processes; continuation of this screen will identify further larval arrest phenotypes. The final aim utilizes a species related to zebrafish that exhibits a natural failure to execute the terminal stages of somatic post-embryonic development. Focusing primarily on the structure and expression within the skin, changes in genetic and developmental architecture will be elucidated in this context of post-embryonic developmental truncation. These analyses will reveal the both extent of decoupling between traits and regulatory pathways, and whether dormant genetic pathways retain responsiveness to a key endocrine mediator of post-embryonic development. Overall, these efforts will characterize the morphogenetic roles of a known endocrine regulator, will identify novel factors that regulate normal post-embryonic progression, and will establish a novel model for dissecting the ways in which developmental genetic pathways and endocrine mechanisms can evolve. Moreover, this project will complete the developmental biology and genetics training of a scholar with a background in population ecology, and will establish establish the foundation for her independent research laboratory.

抽象的 我们仍然对调节和同步形态发生事件的机制知之甚少 脊椎动物发育的后期阶段。但是，了解以后控制这些因素 发展时期对于了解成年特征的形成方式至关重要，并将深入了解 在人类后胎儿和新生儿时期内出现的形态缺陷和疾病。这 研究利用了斑马鱼，该斑马鱼经历了广泛的embryonic发展 许多不同器官系统中的修改和成熟；这些更改中的许多是相似或相同的 到人类胚胎发生后发生的过程。该提案采用了几种策略 了解斑马鱼从幼虫到少年转化的机制。第一个目标 采用有针对性的方法，测试甲状腺激素在胚胎后发育中的特定作用 过渡。多种证据表明甲状腺马酮参与了几种发展 斑马鱼的过程，但是这种赛马实现特异性形态发生过程和细胞的能力 行为仍然不清楚。这个目标将测试甲状腺激素在促进全球体细胞中的作用 发育进展和特定，特征良好的细胞谱系的行为，产生成人 幼虫到少量过渡期间的色素沉着。第二个目标需要一种前瞻性的遗传策略来识别 胚胎后阶段过渡所需的新基因。这种方法已经确定了两个突变体 在幼虫发育期间暴露了完全的体细胞停滞，在各个阶段停止了个体发生的进展 通常以2周和3周的野生型幼虫到达。这些表型表明基因受损 绝对需要胚胎后进展。映射和克隆突变并表征 它们所属的途径将揭示对后胚后发育过程必不可少的机制； 该屏幕的继续将确定进一步的幼虫停滞表型。最终目标利用了相关的物种 斑马鱼表现出自然失败无法执行躯体后的终端阶段 发展。主要关注皮肤内的结构和表达，遗传和 在这种界面后发育截断的情况下，将阐明发展架构。 这些分析将揭示性状和监管途径之间的解耦，以及是否是否 休眠的遗传途径保留了对胚后发育的关键内分泌介质的反应性。 总体而言，这些努力将表征已知内分泌调节剂的形态发生作用，将确定 调节正常胚胎后进展的新因素，并将建立一个新型模型进行解剖 发展性遗传途径和内分泌机制的发展方式。而且，这 项目将完成具有背景的科学的发展生物学和遗传学培训 人群生态学，并将为她的独立研究实验室建立基础。